Low Carb Dietary Treatment of Obesity and Metabolic Syndrome

Low Carb Dietary Treatment of Obesity
and Metabolic Syndrome
Eric C. Westman, M.D. M.H.S.
Director, Lifestyle Medicine Clinic
Associate Professor of Medicine
Department of Medicine
Duke University Medical Center
Durham NC
Course Director, Medical Management of Obesity
President, American Society of Bariatric Physicians
Fellow, The Obesity Society
Author, The New Atkins for a New You
ewestman@duke.edu
Why am I still hungry if I
have all of this extra
stored energy?
Hormonal Theory of Obesity
•
•
Insulin partitions energy into the fat stores.
Insulin “locks in” the energy in the fat store.
Energy In
Energy
Locked In
Why am I still hungry if
I have all of this extra
stored energy?
•
Inability to access stored fat energy
•
Carbohydrate ingestion
raises insulin levels
inhibits fat burning
promotes fat storage
Carbohydrate Restriction Lowers Serum
Insulin Levels and Enhances Lipolysis
•
Sugar raises the serum glucose
•
Starches, like bread and pasta, are digested to glucose and
raise the serum glucose
•
A carbohydrate restricted diet reduces the diet contribution
to serum glucose, which then lowers insulin levels
•
Because insulin is a potent stimulator of lipogenesis (fat
storage), and inhibitor of lipolysis, lowering insulin levels
allows an individual to use their stored body fat
Assumptions About Diets
•
•
Humans must eat 120 grams of carbohydrate daily
•
•
•
•
Low carb diets are “high protein” diets
A low carb ketogenic diet (LCKD) cannot lead to
weight loss because calories aren’t restricted
LCKDs cause “harmful ketosis”
Low carb diets are “hard to maintain”
LCKDs diets increase cardiometabolic risk
Human Essential Nutrients
• Water
• Energy
• Mineral elements
– Major: calcium, phosphorus, potassium, sulfur, sodium, chlorine,
•
•
•
•
magnesium
– Trace: iron, iodine, copper, zinc, manganese, cobalt, chromium,
selenium, molybdenum, fluorine, tin, silicon, vanadium
Amino acids
– Isoleucine, leucine, lysine, methionine, phenylalanine, threonine,
tryptophan, tyrosine, valine
Fatty acids
– Linoleic, linolenic
Vitamins
– Water soluble: thiamine (B1), riboflavin (B2), pyridoxine (B6),
cobalamine (B12), niacin, pantothenic acid, folic acid, biotin, lipoic
acid, vitamin C
– Fat-soluble: vitamins A, D, K, E
Other
– Inositol, choline, carnitine
Harper AE. Defining the essentiality of nutrients. In Shils ME et al, eds. Modern
Nutrition in Health and Disease. Baltimore, William & Wilkins, 1999, pp 3-10.
Daily Carbohydrate Requirements
•
“The lower limit of dietary carbohydrate compatible with
life apparently is zero, provided that adequate amounts of
protein and fat are consumed.”
•
“The minimal amount of exogenous and endogenous carb
is dependent upon the brain (100-140 g glucose/d).”
•
After ketoadaptation, 80% of the CNS energy can be
derived from ketones, leaving 20-28 g glucose/d.
•
“Endogenous glucose production rate: 2-2.5 mg/kg/min ~
2.8 – 3.6 g/kg/day. In a 70 kg man, this represents 210270 g/day.”
Institute of Medicine, Dietary Reference Intakes, 2008
Assumptions About Diets
•
•
Humans must eat 120 grams of carbohydrate daily
•
•
•
•
Low carb diets are “high protein” diets
Low carb diets cannot lead to weight loss because
they don’t explicitly restrict calories
LCKDs cause “harmful ketosis”
Low carb diets are “hard to maintain”
LCKDs diets increase cardiometabolic risk
Diets, Carbohydrates and Calories
Carb grams/day
300
Typical American Diet
Very Low Fat Diet
Low Glycemic Index Diet
200
Mediterranean Diet
Zone Diet
Atkins Maintenance
100
Low Carbohydrate Ketogenic Diet
50
20
0
(Ketonuria)
Diabetes Solution
Atkins Induction
Protein Power
1000
Calories/day
2000
“Good” Carbs
(low-glycemic)
“Bad” Carbs
(high-glycemic)
What Do You Eat on a Low Carb Diet?
Low Carbohydrate Ketogenic Diet
(< 20 grams carbohydrate per day)
•
Eggs, bacon
(or Sugar-free yogurt with berry slices)
•
Chicken Caesar salad
(or Fast Food burger without the bun)
•
Snack: olives, cheese stick
(or pepperoni slices, chicarrones)
•
Steak with bleu cheese, broccoli
(or salmon with cream sauce)
•
Drinks: water, sugar-free drinks, coffee w/cream
Individuals choose foods that they like from a list of low glycemic foods.
Low Carbohydrate Ketogenic Diet
EAT AS MUCH AS YOU WISH OF THE FOLLOWING FOODS:
Meat:
beef, lamb, veal, pork, ham, bacon or any game meat (rabbit, moose, venison)
Poultry: chicken, turkey, duck, pheasant or other game birds
Seafood: any fish or shellfish including but not limited to salmon, halibut, cod, oolichan, crab,
prawns, clams, oysters, mussels, squid, octopus, any smoked, dried or plain canned fish
or seafood (not cured with sugar), roe and roe-on-kelp
Eggs: whole eggs (do not eat whites without yolks)
LIMIT THESE FOODS UNTIL THE DIABETES IS IMPROVED OR ELIMINATED:
Salad Greens: __2__ cups a day. Any leafy vegetable including lettuce or other salad
greens, parsley, spinach, the tops of green onions, sprouts, fiddleheads, seaweed. (If it is
a leaf—you can eat it.)
Vegetables: __1__ cup (measured uncooked) a day. Vegetables that grow above the ground,
including asparagus, beet greens, bokchoy, broccoli, brussel sprouts, cabbage,
cauliflower, celery, chard, Chinese cabbage, cucumber, eggplant, green beans, kale,
leeks, mushrooms, peppers, spinach, string beans, squash, tomatoes, turnips, wax beans
and zucchini.
YOU MUST EAT VEGETABLES EVERY DAY.
Cheese: __4__ ounces a day. Includes hard, aged cheeses such as Swiss, cheddar,
mozzarella, Monterey jack, Gruyere, goat cheese, bleu, feta and soft cheeses such as
cream cheese, brie and camembert. Avoid processed cheeses, cheese spreads or
cheese foods such as Velveeta.
Levels of Low Carbohydrate Diets
•
Phase 1, Induction
– 20 grams of Net Carbs (total carbs minus fiber) per day
•
Phase 2, Ongoing Weight Loss (OWL)
– Each week or several weeks, add 5 daily grams of Net
Carbs, as long as weight loss continues
•
Phase 3, Pre-Maintenance
– Every week or several weeks, add 10 daily grams of Net
Carbs, as long as weight loss continues
•
Phase 4, Lifetime Maintenance
– Continue to consume the number of grams of Net Carbs
that enables weight maintenance and appetite control
Westman EC, Phinney SD, Volek JS. The New Atkins for a New You, 2010.
Outpatient LCKD Randomized Controlled Trials: Design
Reference
Design Setting Patients Duration
Visits
Sondike 2003
RCT
Clinic
Healthy
teens
3m
q2Wk
Brehm 2003
RCT
Clinic
Healthy
adults
6m
q2Wk x 6, then @
6mo
Samaha 2003
Stern 2004
RCT
Clinic
Outpt
adults
6m 12m
qWk x 4, then
monthly
12m
then Wk 26, 34, 42, 52
q2Wk x 2, q4Wk x 4,
Foster 2003
RCT
Clinic
Healthy
adults
Yancy 2004
RCT
Clinic
Healthy
adults
6m
q2Wks x 6, then
monthly
Brinkworth
2009
RCT
Clinic
Healthy
adults
12 m
q2Wks x 4, then
monthly
Nordmann et al. Arch Intern Med 2006;166:285-293.
Outpatient LCKD RCTs: Weight Loss and Serum Lipids
Low Fat
Ref
Low Carbohydrate
Duration
Weight LDL Trig
HDL
Weight
LDL
Sondike
n=30
3 mo
-4.1kg -17%* -6%
+2%
-9.9kg*
+4% -48%* +4%
Brehm
n=42
6 mo
-3.9kg† -5% +2%
+8%
-8.5kg*†
0%
Samaha/ 6 mo
Stern
12 mo
n=132
-1.9kg† +3% -4% -2%
-3.1kg -3% +2% -12%
-5.8kg*†
-5.1kg
+4% -20%* 0%
+6% -29% -2%
Foster
6 mo
-5.3kg† -3% -13% +4%
-9.7kg*†
+4%
n=63
12 mo
-4.5kg† -6% +1%
+3%
-7.3kg†
+1% -28%* +18%*
Yancy
n=119
6 mo
-6.5kg
-3% -15% -1%
-12.0kg*
+2% -42%* +13%*
-14.5kg
+3%
Brinkworth 12 mos -11.5kg +3% -12%
N=40
* p<0.05 for between-groups comparison
0%
Trig
HDL
-23%* +13%
-21% +20%*
-35% +21%
Examples of Diet Programs
 DASH: Dietary Approaches to Stop Hypertension

A diet with no extreme percentages of macronutrients; low in sugar, salt, alcohol and saturated fat,
with moderate levels of total fat, and a high level of mono-unsaturated fats. It emphasizes helpful
minerals and antioxidants to lower blood pressure.
 Ornish

Very high carbohydrate vegetarian diet, extremely low fat, moderate protein. It advises: unlimited
quantities of low-fat, high-fiber, complex CHO foods, such as beans, legumes, fruits, vegetables,
and grains. Low fat dairy products are allowed in moderation. The following are prohibited: meats,
eggs, nuts, oils, seeds, alcohol, and high fat fruits and vegetables.
 The Zone Diet

40% C, 30% P, 30% F; focuses on lean meats (especially poultry), avoids high-fat animal products
(fatty meats, dairy products, eggs), as well as most grain products, starchy vegetables, and some
fruits.
 South Beach Diet

28% C, 33%P, 39% F; emphasizes healthy carbs, such as whole grains and certain fruits and
vegetables; mono-unsaturated fats, such as olive and canola oil and nuts; and lean sources of
protein.
 Atkins
•
6% C, 35% P, 59% F; carbohydrate-restricted, adequate protein, high-fat diet; 1 cup of nonstarchy
vegetables, 2 cups of leafy greens at early, during most restrictive phase.
 Mediterranean

40% C, 17% P, 43% F; high amount of mono-unsaturated fats. The diet contains: vegetables, fruits,
cereals, dairy products, meats and poultry, fish, wine, legumes, and olive oil – in that order.
Workplace Diet Trial
322 workers at Israeli research center, BMI >27 kg/m2
R
Low Fat Diet
Mediterranean Diet
Low Carb Diet
• <30% fat
• Calorie-
• <35% fat
• Calorie-
• <20 g/day carbs
restricted
• Grains, vegies,
fruits, legumes
restricted
• Add fish, nuts,
olive oil
initially
• Increase to max
of 120 g/day
• No calorie
restriction
Shai I et al. New Engl J Med 2008;359:229-41.
A Comparison of Three Diets
Shai I. N Engl J Med 2008;359:229-41.
Workplace Diet Trial:
Serum Tests
Test
Low Fat
Mediterranean
Low Carb
Systolic BP, mm Hg
-4.3
-5.5
-3.9
Diastolic BP, mm Hg
-0.9
-2.2
-0.8
LDL-C, mg/dl
-0.05
-5.6
-3.0
HDL-C, mg/dl
6.3
6.4
8.4
Triglyceride, mg/dl
-2.8
-21.8
-23.7
T Chol : HDL ratio
-0.6
-0.9
-1.1
Hemoglobin A1c, %
-0.4
-0.5
-0.9
C-reactive protein, mg/l
-0.6
-0.9
-1.3
Yellow denotes p<0.05 for within-group change from baseline.
Blue denotes p<0.05 for comparison of Low Carb vs Low Fat.
Circulation. 2010;121:1200-1208.
A Comparison of Four Diets
Dansinger ML. JAMA 2005;293:43--53.
A Comparison of Four Diets
Gardner C. JAMA 2007;297:969-77.
Insulin Resistance and Diet Success
Re-examination of the A to Z Study [Gardner et al. JAMA 2007]
Women divided into tertiles based on insulin resistance
Weight loss at 12 mo:
Simply put, insulin
resistance strongly
influences how we respond
to different diets
Validates the concept that
insulin resistance is
essentially an expression of
carbohydrate intolerance
Low Carb
Low Fat
Insulin
Resistant -11.9 lbs
-3.3 lbs
Insulin
Sensitive
-9.0 lbs
-11.7 lbs
Gardner, C.D., et al., Insulin Resistance - An Effect Moderator of Weight Loss
Success on High vs. Low Carbohydrate Diets. Obesity, 2008. 16: p. S82.
Low Fat Diet Reduces LDL-C
Low Carb Diet Targets Trig/HDL
Serum LDL-C:
Serum Triglyceride:
Nordmann et al. Arch Intern Med. 2006;166(3):285-293.
Meta-analysis of RCTs
Comparing Low-carb to Low-fat Diets
•
“Low-carbohydrate/high-protein diets are more
effective at 6 months and are as effective, if not
more, as low-fat diets in reducing weight and
cardiovascular disease risk up to 1 year.”
Hession M, Rolland C, Kulkami U, Wise A, Broom J. Systematic review of randomized controlled
trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its
comorbidities. Obes Rev 2009;10:36-50.
Mediterranean Diet
 Whole grains, fruits, vegetables, legumes, nuts,
monounsaturated oil (olive oil, avocados, etc)
 Fish and seafood, moderate alcohol
 Limited poultry, dairy, red meat infrequent
 PREDIMED Study

30% lower risk of first cardiovascular event
Lyon Heart Study
- 50%-70% lower risk of recurrent CHD
-
.
Estruch R et al. NEJM 2013;368:1279-190
de Lorgeril M et al. Circulation 1999;99:779-85.
Low Carb vs. Low Fat Diet + Orlistat
Study Design
146 overweight VA outpatient volunteers
R
Low Fat Diet + Orlistat
Low Carb Ketogenic Diet
•
•
•
•
• group meetings for 48 wks
• exercise recommendation
• multivitamin daily
group meetings for 48 wks
exercise recommendation
multivitamin daily
Orlistat (Xenical™) 120 mg
three times a day
Yancy WS Jr. et al. Arch Int Med 2010;170:136-45.
Mean % Weight Change Over Time*
Orlistat + Low Fat Diet
Low Carbohydrate Diet
n=
65
n=
57
74
71
66
65
60
61
69
61
52
53
46
54
72
64
58
58
51
50
57
48
43
54
41
40
Change in Blood Pressures at 3 Time points
Change in Blood Pressure by Treatment Arm
2
1
0
-1
ΔmmHg
-2
-3
P
B
D
P
B
S
LCKD
P
B
D
P
B
S
O+LFD
-4
-5
-6
-7
Yancy WS Jr. et al. Arch Int Med 2010;170:136-45.
Δ at 4 weeks
Δ at 24 weeks
Δ at 48 weeks
4 wks (-0.5 v.+0.1; p<.001)
24 wks (-3.0 v.+0.7; p<.001)
48 wks (-5.9 v.+1.5; p<.001)
Low Carbohydrate Diet Program and
Triglycerides/HDL
Before Diet
After Low Carb Pgm
Age Sex Duration Weight A1C Trig HDL
35
37
50
57
33
57
37
74
50
48
F
F
M
M
M
M
F
M
M
F
5 mos
7 mos
13 mos
14 mos
21 mos
21 mos
22 mos
25 mos
26 mos
28 mos
(lb)
188
154
245
245
290
231
168
250
275
156
11.3
4.8
10.9
6.2
8.9
9.8
5.1
9.0
-
503
1368
735
370
646
510
651
522
6500
2407
27
29
31
51
36
42
19
40
20
Weight A1C Trig HDL
(lb)
175
215
227
293
212
140
198
215
156
6.3
5.3
5.3
6
5.2
5.8
5.3
5.3
-
145
243
329
114
166
48
172
60
329
84
41
60
37
60
38
69
31
66
37
37
Diabetic Diet in the Pre-Insulin Era
1914-1921
“Quantity of food required by a severe diabetic patient weighing 60
kilograms”*
Food
Calories
Carbohydrate
10 grams
40
Protein
75 grams
300
Fat
150 grams
Alcohol
15 grams
1,350
105
1,795
“Strict diet”: Meats, poultry, game, fish, clear soups, gelatin, eggs, butter,
olive oil, coffee, tea
* Osler W, McCrae T. The Principles and Practice of Medicine. NY: Appleton and Co., 1923.
Allen FM. Protein diets and undernutrition in treatment of diabetes. JAMA 1920;74:571-577.
Newburgh LH, Marsh PL. The use of a high fat diet in the treatment of diabetes mellitus. Arch Int Med
1921;27:699-705.
“Spoonful of sugar
in entire human bloodstream”
Glucose meter = 100 mg/dL
5-7 liters of blood in the body
4 g/tsp sugar so 5-7g = “heaping spoonful”
100 mg
10 dL 1 grams
----------- * ----------- * -------- * 7 L blood = 7 grams
dL
L
1000 mg
Glucose meter = 100 mg/dL
5-7 liters of blood in the body
4 g/tsp sugar so 5-7g = “heaping spoonful”
// /
/
//
/
100 mg
10 dL 1 grams
----------- * ----------- * -------- * 7 L blood = 7 grams
dL
L
1000 mg
// / /
/
5-7 grams of glucose
in human bloodstream
The Effect of a Low-carbohydrate, Ketogenic Diet Versus a Lowglycemic Diet on Glycemic Control in Type 2 Diabetes Mellitus
Overweight or
obese
volunteers
with type 2
diabetes
R
Low Glycemic Index Diet
(LGI) instruction
+ group meetings
+ exercise recommendation
+ nutritional supplements
Low Carbohydrate
Ketogenic Diet (LCKD)
instruction
+ group meetings
+ exercise recommendation
+ nutritional supplements
Westman et al. Nutrition & Metabolism 2008;5:36.
Primary Outcome: Hemoglobin A1c
LCKD
LGI
13
12
Hemoglobin A1c, %
Hemoglobin A1c, %
13
11
10
9
8
7
12
11
10
9
8
7
6
6
5
5
Baseline
12 Weeks
LGI (n=29)
HgbA1c, %
24 Weeks
Baseline
12 Weeks
24 Weeks
Baseline
12 Weeks
24 Weeks
Base24
mean (sd)
mean (sd)
mean (sd)
change, %
8.3 (1.9)
7.5 (1.7)
7.8 (2.1)
-0.5 (-6.0%)*
8.8 (1.8)
7.2 (1.2)
7.3 (1.5)
-1.5 (-17.0%)*
LCKD (n=21)
HgbA1c, %
*p <0.05 between groups
Westman et al. Nutrition & Metabolism 2008;5:36.
Effect of Diet Programs on Metabolic Syndrome Parameters
LGI (n=29)
LCKD (n=21)
Week 0
Week 24
Change
Week 0
Week 24
Change
mean
mean
mean
mean
mean
mean
Fasting glucose,
mg/dL
166.8
150.8
-16.0*
178.1
158.2
-19.9*
Waist
circumference, in.
47.0
42.4
-4.6 *
47.1
41.8
-5.3 *
Triglycerides,
mg/dL
167.1
147.8
-19.3
210.4
142.9
-67.5 *
HDL cholesterol,
mg/dL
48.7
48.7
-0 †
44.0
49.6
+5.6 * †
Systolic blood
pressure, mmHg
140.8
130.1
-10.7 *
144.4
127.8
-16.6 *
Diastolic blood
pressure, mmHg
84.1
78.5
-5.6 *
83.9
75.8
-8.1 *
Body mass index,
kg/m2
37.9
35.2
-2.7 * †
37.8
33.9
-3.9 * †
* p < 0.05 for within-group change from Week 0 to Week 24.
† p < 0.05, for between groups change from Week 0 to Week 24.
Facts About Low Carbohydrate, High Fat
Diets
•
•
Carbohydrate is not an essential nutrient
•
•
•
•
Low carb diets are adequate protein diets
Low carb diets lead to weight loss because
abnormal hunger/appetite goes away
Nutritional ketosis is a marker of burning fat
For many people low carb diets are easy to follow
LCKDs diets reduce cardiometabolic risk by
addressing the metabolic syndrome
Does Insulin Reduction Explain the Lack of
Rise in Serum Cholesterol?
Kennedy AR et al. A high fat, ketogenic diet induces a unique metabolic state in
mice. Am J Physiol Endocrinol Metab 2007, February 13.
Saturated Fat is Processed Differently Under Different
Metabolic Conditions
Low Fat Diet
(208 g CHO/d)
Saturated Fat
Synthesis
Saturated Fat
Saturated Fat
Intake (12 g/d)
Saturated Fat
Burned as Fuel
Low Carbohydrate Diet
(45 g CHO/d)
Saturated Fat
Synthesis
Saturated Fat
Intake (36 g/d)
Saturated
Fat
Saturated Fat
Burned as Fuel
Forsythe et al. Lipids. 43(1):65-77, 2008
Fat
Diet:
Triglycerides
Lipids
Observed
Very Low
Carb Diet
Liver
Large LDL
Chylomicrons
Lymphatics
Thoracic Duct
Superior Vena Cava
Triglyceride
Atherosclerosis?
Cells
Diet:
Carbohydrate
Lipids
Observed
Mixed Diet
Fat
Simple sugars
Triglycerides
Portal Vein
Chylomicrons
Sugar
Liver
Lymphatics
Triglyceride
LDL
VLDL
LDL
Small LDL
Atherosclerosis
Thoracic Duct
Superior Vena Cava
Triglyceride
Cells
Weight Loss, Improvements in Lipids
A 50 year old white female with obesity (BMI = 31.3) wants to lose
weight.
Fasting lab tests:
Date
BMI
Wt (lbs)
Chol
Trig
LDL
HDL
Glucose
6/10
31.3
178
245
247
141
54
92
81
88
Initiation of Carbohydrate Restricted Diet
8/10
29.1
164
2/11
24.5
141
5/11
23.5
138
209
46
119
She asks, “Why wasn’t I given this option before? I was just given the
options of medications.”
Reduction in Belief in the Low-fat Diet
•
Low-fat diet recommendations started in a
political subcommittee and then were never
proven useful in subsequent studies
•
Dietary intervention study of 48,000 women
using a low-fat had no effect on breast cancer,
colorectal cancer, or heart disease
Taubes, G. Good Calories, Bad Calories. Anchor, 2008.
Prentice et al. Low-fat dietary pattern and risk of invasive breast cancer. The Women’s
Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295:629642. Beresford et al. JAMA 2006;295:643-654. Howard et al. JAMA 2006;295:655-666.
Summary
•
Instructing people to limit carbohydrate grams leads
to a spontaneous reduction in caloric intake (without
explicitly limiting calories) and:
Loss of body weight
Improvements in fasting serum lipid profiles (triglyceride,
HDL, chol/HDL ratio)
– Improvement in systolic blood pressure
– Reduction in waist circumference
–
–
•
Low carbohydrate diets can be used in the clinical
setting by trained practitioners
•
A low carbohydrate diets is the preferred diet for
metabolic syndrome
Low Carb Dietary Treatment of Obesity
and Metabolic Syndrome
Eric C. Westman, M.D. M.H.S.
Director, Lifestyle Medicine Clinic
Associate Professor of Medicine
Department of Medicine
Duke University Medical Center
Durham NC
Course Director, Medical Management of Obesity
President, American Society of Bariatric Physicians
Fellow, The Obesity Society
Author, The New Atkins for a New You
ewestman@duke.edu